1. Introduction We comment to request a reconsideration and extension of the current deadline for compliance with the revised USP Chapters <795> and <797> for 503A compounding pharmacies to November 1st, 2024.

2. Reason for Request Due to ongoing and significant challenges faced by the pharmaceutical industry, including extended delays from laboratories in performing stability studies and terminal sterilization, as well as persistent supply chain disruptions, we propose the Board discuss an extension of the deadline to November 1, 2024. These challenges have created a complex operating environment, hindering our ability to comply within the current timeline and will ultimately lead to a negative impact on patient care.

3. Impact of Delays The delays in laboratory services are not only affecting the timely compliance with the new standards but also impacting the overall quality and safety measures that these revisions aim to uphold. Furthermore, supply chain issues have led to a scarcity of critical materials and equipment (agar plates, air samplers, non-viable particle samplers, biological/chemical indicators) necessary for adherence to the revised chapters.

4. Importance of Compliance While we fully support the intent and importance of the USP revisions in ensuring the highest standards of quality and safety in compounding practices, the current timeline imposes considerable strain on our resources and operational capabilities, and ultimately on patient care.

5. Proposed Solution An extension of the compliance deadline to November 1, 2024, would provide the necessary time for compounding pharmacies to adapt effectively to these changes, ensuring that compliance is achieved without compromising on quality or safety standards.

6. Conclusion In light of these challenges, we respectfully request the Board to consider this extension, which we believe is in the best interest of both the pharmaceutical industry and the patients we serve. We appreciate the Board’s understanding and support in these unprecedented times.

Thank you for the opportunity to comment on document 110-36. In the new USP there are changes that will enhance compounding quality and patient safety, however there are several arbitrary changes that will not. I wanted to voice my concern on these changes relevant to the new USP along with document 110-36.

The compounding Expert Committee (CEC) of the U.S. Pharmacopeia (USP) has introduced revised chapters 795 and 797 that became effective November 1^st, 2023. In several of the recommendations the CEC has not enunciated the scientific basis for the restrictions or how those restrictions keep patients safer. This is a deviation from the CEC from the norm with an independent organization like USP, whose credibility should be rooted in hard data to document the standards that it issues. These restrictions, that are not based on scientific data, create impediments to patient access to certain compounded sterile preparations.

As the state board of pharmacy, it is imperative that the board is aware and has considered all of the implications of certain unsubstantiated restrictions on patient safety and access in Virginia.

Below are proposed changes to USP that should not be implemented without thoughtful consideration of the Virginia Board of Pharmacy:

1. USP 797 beyond-use dating
2. USP 797 batch size restriction
3. USP 797 increase environmental monitoring

Moreover, items that I believe need clarity in document 110-36 are listed below:

1. Define enforcement discretion from the Board’s perspective in regard to flavoring
   1. I believe transparency is key to ensure that pharmacists understand the expectation from the Board and practice accordingly.
2. Change that the Board will exercise enforcement discretion for the first 6 months from the date the revised document 110-36 is adopted.
   1. I believe that discretion should be from the adoption of the document as this is the Board’s official statement on USP and until the revised document is adopted there is not an official document for pharmacists to reference stating the Board’s views on the new USP while practicing pharmacy in Virginia

USP 797 beyond-use dating, batch size restriction and increased environmental monitoring:

USP 797 restricts batch sized for compounded sterile product (CSPs) to 250 units and limits beyond-use dates of these compounds without providing evidence that the new restrictions enhance patient safety by reducing the risk of contamination. 250 units is an arbitrary batch size limit. Moreover, limiting the batch size could potentially increase contamination. With a reduced batch size compounders will now need to prepare multiple batches instead of fewer larger batches, increasing the number of manipulations and foot traffic inside sterile environments. Furthermore, increased activity may increase fatigue for the compounder and may lead to poor aseptic technique. Financially the requirement of more batches increases cost associated in preparing the medications which will ultimately result in higher costs for patients. The CEC has provided no data that the implementation of the batch size limit, which doubles the percentage of units tested per batch, will increase the probability of detecting a contaminated sample. In addition, the CEC has provided no explanation why the new guidelines restrict the batch size rather than increasing the minimum number of required samples for a batch regardless of batch size.

Another new restriction in the current USP 797 is a limit on beyond-use dating to less than 180 days with no scientific basis for the restriction. This restriction will require compounders to compound CSPs more frequently to meet patient need, increasing the number of batches. Also, shorter BUDs will mean that patients must get refills more frequently, increasing patient inconvenience and increasing the risk that a patient may not stay adherent to their drug therapy.

The CEC has acknowledged the need for CSPs to be assigned a BUD of up to 180 days but missed the mark allowing category 3 CSPs in general to be assigned a BUD of up to 180 days and instead only allows on type of category 3 CSP (terminally sterilized, stored frozen) a maximum BUD of 180 days. The need in today’s healthcare system for CSPs with extended BUDs up to 180 days goes beyond just terminally sterilized CSPs stored frozen, it is a need that applies to aseptically processed CSPs and CSPs stored refrigerated and at room temperature as well. For example, compounders have been making both progesterone and testosterone injectable medication in oil with years of data showing stability and safety stored at room temperature with BUDs of 180 days or more. The newly imposed restrictions from USP 797 regarding beyond use dating restricts a compounder to make a now inferior product. For example, if a compounder wanted to make testosterone in oil with a BUD dating of up to 180 days it would have to be labeled with frozen conditions. Testosterone’s solubility is directly correlated with temperature and at lower temperatures it crystalizes. Thus, the ideal storage temperature is controlled room temperature and frozen testosterone would be an inferior product. This restricts the compounder to put a shortened room temperature BUD per the newly implemented guidelines. This will again increase cost, decrease patient adherence and overall, negatively impact patients in Virginia without any scientific basis.

In summary I ask the Virgnia Board of Pharmacy to consider rejecting the new USP 797 beyond use dating and batch size restrictions in favor of the previous USP 797 requirements. Or at a minimum to put out guidance to the commonwealth that the board will exercise enforcement discretion while considering batch size and BUD dating. Compounders who have invested and created a contamination control strategy and stability program that includes environmental monitoring sampling to eliminate many of the concerns CEC may have should not be handicapped while trying to serve their patients in Virginia. I feel that it is important that the Virginia Board of Pharmacy be aware of all USP’s potential flaws and lack of scientific data to make an informed decision to overall benefit and protect the patients in the commonwealth. Ultimately adopting USP 797 in its entirety without careful consideration from the Virginia Board of Pharmacy on the practical and patient facing implications, introducing greater risk and cost into the sterile compounding process. I appreciate your attention on this important matter.

Thank you for the opportunity to comment on Guidance Document 110-36

Regarding Question 5

Can the Board consider allowing pharmacies with common ownership to transfer compounded preparations among those stores if the company maintains a real time shared inventory database?

Physicians are really struggling to find compounded products to use at the chair level (see examples). The 503B pharmacies are not making these items to sell as office stock and the offices also do not want to get permits to store drugs. These are small amounts of items that are used for occasional patient procedures. There could be Qty limits if that helps ensure this doesn’t become “office stock”. Can the Board find regulatory language for non-sterile compounded preparations that allows us to help these patients while not breaking the FDA’s rules.

• Examples:

  • Sinus procedures - there is a need for anesthetic nasal sprays prior to scope or in office procedure. 

  • Otic powder that is sprayed into the ear canal after an ear is cleaned and an infection is suspected.

  • OB/Gyn, Derms and Dentists need anesthetic creams/sprays for exams, excisions, and other minor in office procedures.

Consideration to add additional questions:

Because of the new USP requirements the chain stores and independent pharmacies have abandoned compounding entirely. There are now towns where there is no access to what I call simple compounding. Consider making an allowance outside of full compliance with USP 795 for the mixing of manufactured products. For example a magic mouthwash formulation is a simple combination of 3-4 ingredients poured together. They are not hazardous to the person mixing and don’t require any specialized equipment. Another example is basic butt paste, or antifungal/steroid cream combinations. This allows for affordability and access for patients in a timely manner.

An awareness of USP 797 BUDs and testing implications:

As a compounding pharmacist with over 20 yrs experience in sterile compounding, I want to bring to your attention a hypothetical scenario that has patent safety concerns. The new guidelines allow Semaglutide to be compounded in a batch of 250 units. It is aseptically compounded, not terminally sterilized and can be given a 45 day frozen expiration date with NO testing required. Sterility is a probability principle, the larger the batch the more likely it can be contaminated. I would recommend that the board make an exception that is similar to the previous USP, that any batch over 24 units should be tested for sterility and endotoxins.   

Commentary:

Compounding is inherent to our profession, but the principle of working with a prescriber to make something specific for a patient has gone by the wayside. When a pharmacist's discretion combined with research and published data is thrown out, our profession is diminished. Requiring stability indicating assays that cost $50,000+ per formulation is just plain wrong for formulations that have been listed for years in resources like Trissels and the Pediatric Handbook.

Overall, my ask related to this document, but not directly addressed in the questions, is to consider an addendum to the USP; thereby allowing safe and accessible medications to our VA residents. Many states have chosen not to adopt USP standards. I am not asking for that, but there must be a way to have some flexibility or exceptions that allow us to take care of our patients and maintain access to affordable compounds.  

Thank you for your time.